The Legacy of Patient H.M. for Neuroscience
Larry R. Squire1,2,*
Affairs Healthcare System, San Diego, CA 92161, USA of Psychiatry, Neurosciences, and Psychology, University of California, San Diego, La Jolla, CA 92093, USA *Correspondence: firstname.lastname@example.org DOI 10.1016/j.neuron.2008.12.023 2Departments 1Veterans
H.M. is probably the best known single patient in the history of neuroscience. His severe memory impairment, which resulted from experimental neurosurgery to control seizures, was the subject of study for ﬁve decades until his death in December 2008. Work with H.M. established fundamental principles about how memory functions are organized in the brain.
In 1952, Brenda Milner was completing her doctoral research at McGill University under the direction of Donald Hebb. At about this time, she encountered two patients (P.B. and F.C.) who had become severely amnesic following unilateral removal of the medial structures of the left temporal lobe for the treatment of epileptic seizures (Penﬁeld and Milner, 1958). This unfortunate outcome was entirely unexpected, and it was proposed that in each case there had been a preexistent, but unsuspected, atrophic lesion in the medial temporal lobe of the opposite hemisphere. In that way, the unilateral surgery would have resulted in a bilateral lesion, an idea that was conﬁrmed at autopsy some years later for patient P.B. After the two cases were presented at the 1955 meeting of the American Neurological Association, Wilder Penﬁeld (the neurosurgeon in both cases) received a call from William Scoville, a neurosurgeon in Hartford, Connecticut. Scoville told Penﬁeld that he had seen a similar memory impairment in one of his own patients (H.M.) in whom he had carried out a bilateral medial temporal lobe resection in an attempt to control epileptic seizures. As a result of this conversation, Brenda Milner was invited to travel to Hartford to study H.M. H.M. had been knocked down by a bicycle at the age of 7, began to have minor seizures at age 10, and had major seizures after age 16. (The age of the bicycle accident is given as 9 in some reports; for clariﬁcation see Corkin, 1984.) He worked for a time on an assembly line but, ﬁnally, in 1953 at the age of 27 he had become so incapacitated by his seizures, despite high doses
of anticonvulsant medication, that he could not work or lead a normal life. Scoville offered H.M. an experimental procedure that he had carried out previously in psychotic patients, and the surgery was then performed with the approval of the patient and his family. When Milner ﬁrst visited H.M., she saw that the epilepsy was now controlled but that his memory impairment was even more severe than in Penﬁeld’s two patients, P.B. and F.C. What she observed was someone who forgot daily events nearly as fast as they occurred, apparently in the absence of any general intellectual loss or perceptual disorder. He underestimated his own age, apologized for forgetting the names of persons to whom he had just been introduced, and described his state as ‘‘like waking from a dream . every day is alone in itself.’’ (Milner et al., 1968, p. 217). The ﬁrst observations of H.M., and the results of formal testing, were reported a few years later (Scoville and Milner, 1957). This publication became one of the most cited papers in neuroscience (nearly 2500 citations) and is still cited with high frequency. H.M. continued to be studied for ﬁve decades, principally by Brenda Milner, her former student Suzanne Corkin, and their colleagues (Corkin, 1984, 2002; Milner et al., 1968). He died on December 2, 2008, at the age of 82. It can be said that the early descriptions of H.M. inaugurated the modern era of memory research. Before H.M., due particularly to the inﬂuence of Karl Lashley, memory functions were thought to be widely distributed in the cortex and to be integrated with intellectual and perceptual functions.
The ﬁndings from H.M. established...